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Titel: A hydrogel-based in vitro assay for the fast prediction of antibiotic accumulation in Gram-negative bacteria
VerfasserIn: Richter, Robert
Kamal, Mohamed A. M.
García-Rivera, Mariel A.
Kaspar, Jerome
Junk, Maximilian
Elgaher, Walid A. M.
Srikakulam, Sanjay Kumar
Gress, Alexander
Beckmann, Anja
Grißmer, Alexander
Meier, Carola
Vielhaber, Michael
Kalinina, Olga
Hirsch, Anna K.H.
Hartmann, Rolf W.
Brönstrup, Mark
Schneider-Daum, Nicole
Lehr, Claus-Michael
Sprache: Englisch
Titel: Materials Today Bio
Bandnummer: 8
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2020
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The pipeline of antibiotics has been for decades on an alarmingly low level. Considering the steadily emerging antibiotic resistance, novel tools are needed for early and easy identification of effective anti-infective compounds. In Gram-negative bacteria, the uptake of anti-infectives is especially limited. We here present a surprisingly simple in vitro model of the Gram-negative bacterial envelope, based on 20% (w/v) potato starch gel, printed on polycarbonate 96-well filter membranes. Rapid permeability measurements across this polysaccharide hydrogel allowed to correctly predict either high or low accumulation for all 16 tested anti-infectives in living Escherichia coli. Freeze-fracture TEM supports that the macromolecular network structure of the starch hydrogel may represent a useful surrogate of the Gram-negative bacterial envelope. A random forest analysis of in vitro data revealed molecular mass, minimum projection area, and rigidity as the most critical physicochemical parameters for hydrogel permeability, in agreement with reported structural features needed for uptake into Gram-negative bacteria. Correlating our dataset of 27 antibiotics from different structural classes to reported MIC values of nine clinically relevant pathogens allowed to distinguish active from nonactive compounds based on their low in vitro permeability specifically for Gram-negatives. The model may help to identify poorly permeable antimicrobial candidates before testing them on living bacteria.
DOI der Erstveröffentlichung: 10.1016/j.mtbio.2020.100084
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/pii/S2590006420300442
Link zu diesem Datensatz: hdl:20.500.11880/30846
http://dx.doi.org/10.22028/D291-33539
ISSN: 2590-0064
Datum des Eintrags: 11-Mär-2021
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Pharmazie
NT - Systems Engineering
Professur: NT - Prof. Dr. Claus-Michael Lehr
NT - Prof. Dr. Michael Vielhaber
NT - Prof. Dr. Anna Hirsch
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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